Antimicrobial - Various Herbs

http://www.dcmsonline.org/jax-medicine/2001journals/Feb2001/herbs.htm

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Antimicrobial Herbs

Thomas M. Bozzuto, D.O.,
Medical Director, Mind/Body Institute

Estimates are that, by 2010, nearly two-thirds of the United States population will be using some form of Complementary and Alternative Medicine (CAM)¹. Many of the self-treatments are for presumed or actual infectious processes (colds, flu, etc.). The physician who wishes to offer a patient herbal options for antimicrobial agents has several options to choose from.

Goldenseal (Hydrastis canadensis) contains a high content of isoquinoline alkaloids, of which berberine is the most widely studied. Although not as potent as some prescriiption antibiotics, berberine exhibits a broad spectrum of antibiotic activity. It has also shown activity against protozoa and fungi.^2-4 Antimicrobial activity increases with pH in all organisms studied.³ Alkalinization will improve its clinical efficacy particularly in the treatment of urinary tract infections. Berberine has also been shown to activate macrophages.⁵ Usual dose is 250-500 mg/day (8-12% alkaloid content). Berberine is generally non-toxic at recommended doses, but it is not recommended for use during pregnancy, and it can decrease B vitamin absorption. It may interfere with H-2 antagonists, proton pump inhibitors, antihypertensives, barbiturates and sedatives, and heparin.^6,7

Echinacea (Echinacea angustifolia or purpurea) has been the subject of over 200 scientific studies.^8,9 Echinacea is the most widely recommended herb for infectious conditions despite the fact that the direct activity of Echinacea as an antibacterial is quite mild. Its main effect appears to be immunostimulatory; activating the alternative complement pathway, promoting chemotaxis of neutrophils, monocytes, and eosinophils, enhancing macrophage phagocytosis and stimulation of production of TNF, interferon, and interleukin-1.^10-12 The herb also possesses antiviral activity due to inhibition of hyaluronidases.¹³ It has been shown to decrease symptoms and length of sickness in patients experiencing the common cold.¹⁴ Echinacea has also been shown to accentuate the topical antimycotic agent (econazol nitrate) decreasing recurrence of C. albicans from 60.5% to 5-16.7%.¹⁵

The usual dose is 900 mg/day of 3.5% echinacoside. Caution is indicated in patients with HIV because of potential stimulation of viral replication. The literature on Echinacea has been reviewed by the Cochrane Collaboration. The reviewers concluded that the majority of available studies report positive results.¹⁶

St. John's Wort (Hypericum perforatum) has received national attention as an herbal anti-depressant. Surprisingly, it is most effective as an anti-vial and anti-bacterial. In vitro studies have shown that the two major compounds (hypericin and pseudohypericin) exhibit strong antiviral activity against HSV I and II as well as influenza types A and B, vesicular stomatitis virus and remarkable antiviral activity against Epstein-Barr virus.^{17, 18} St. John's Wort also have broad spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria including Staphylococcus aureus, Streptococcus mutans, Proteus vulgaris, E. coli, and Pseudomonas aeruginosa.¹⁹ Research suggests that Hypericum may be a useful adjunctive treatment for herpes simplex, mononucleosis, and influenza, and because of its antidepressant and anti-EBV activity, a promising treatment for fibromyalgia and chronic fatigue. Several studies show effectiveness of Hypericum against HIV.^20-22

St. John's Wort has a historical use as an topical aid to wound healing. Research has demonstrated antibacterial and wound healing activity.²³ The usual oral dose of Hypericum standardized to 0.3% hypericin is 300 mg three times a day. There are many potential drug interactions, including: sedative-hypnotics, 5-HT antagonists, cyclosporine, digoxin, nefazodone, NNRTI's, tricyclic antidepressants, photosensitizing drugs, protease inhibitors, theophylline, and coumadin. Hypericum is metabolized by the cytochrome P-450 system and caution should be used with any drugs using the same metabolic pathway.

Licorice root (Glychrrhiza glabra) has, as its major active component a triterpenoid saponin, glycyrrhizic acid. Intestinal flora hydrolyzes glycyrrhizin yielding the aglycone molecule (glycyrrhentinic acid) and a sugar moiety, resulting in absorption of both.²⁴ Both glycyrrhizin and glycyrrhentinic acid have been shown to induce interferon.²⁵ This leads to significant antiviral activity. Licorice root has been shown to directly inhibit the growth of several DNA and RNA viruses in cell cultures (vaccinia, herpes simplex, Newcastle disease, vesicular stomatitis virus) and to irreversibly inactivate HSV I.²⁶ The herb also shows antimicrobial activity in vitro against Staphylococcus aureus, Streptococcus mutans, Mycobacterium, and Candida albicans.²⁷ Licorice compounds are showing promise in the treatment of HIV related diseases and chronic Hepatitis B (40% of patients will have complete resolution).^28,29 Topical preparations have been shown to reduce the healing time and pain associated with cold sores, apthous ulcers, and genital herpes.^30,31 Caution is recommended when used with drugs that can deplete potassium, stimulant laxatives, and herbs with anticoagulant/antiplatelet properties, including: aspirin and other NSAID's, corticosteroids, cardiac glycosides, loop diuretics, hormones (estrogen-like), insulin, MAOI's and interferon. The use of deglycyrrhizinated licorice (DGL) is recommended because of comparable efficacy but reduced side-effects. Usual dose of standardized 4% extract is 250-500 mg/day.

Other herbs exist which show definite but more limited antimicrobial activity. One such example is Uva ursi (bearberry, upland cranberry) which is especially active against E. coli and can be used in the acute treatment and prevention of recurrent cystitis. It is also active against C. albicans and S. aureus. The usual dose of extract standardized to 10% arbutin is 250-500 mg/day.³²

References

1. Institute for Alternative Futures. The Future of Complementary and Alternative Approaches (CAAs) in US Health Care. Alexandria VA, 1998.
2. Hahn FE, Ciak J. Berberine. Antibiotics 1976;3:577-588.
3. Amin AH, Subbaiah TV. Abbasi KM. Berberine sulfate. Antimicrobial activity, bioassay, and mode of action. Can J Microbiol 1969;15:1067-1076.
4. Kaneda Y, et al. In vitro effects of berberine sulfate on the growth of Entamœba histolytica, giardia lamblia, and Trichomonas vaginalis. Annals Trop Med Parasitol 1991;85:417-425.
5. Kumazawa Y, Itagaki A, Fukumoto M, et al. Activation of peritoneal macrophages by berberine alkaloids in terms of induction of cytostatic activity. Int J Immunopharmacol 1984;6:587-592.
6. Newall CA, Anderson LAPhilpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: Pharmaceutical Press, 1996.
7. Brinker F. Herb Contraindications and Drug Interactions. 2^nd ed. Sandy, OR:Eclectic Medical Publications, 1998.
8. Hobbs C. The Echinacea Handbook. Portland, OR: Eclectic Medical Publications, 1989.
9. Bauer R, Wagner H. Echinacea species as potential immunostimulatory drugs. Econ Med Plant Res 1991;5:253-321.
10. Wagner V, Proksch A, Reiss-Maurer I, et al. Immunostimulating polysaccharides (heteroglycans) of higher plants. Arzneim Forsch 1985;35:1069-1075.
11. Stimpel M, Proksch A, Wagner H, Lohmann-Matthes ML. Macrophage and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpuera. Infection Immunity 1984;845-849.
12. Luettig B, Steinmuller C, Gifford GE, et al. macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Nat Cancer Inst 1989;81:669-675.
13. Wacker A, Hilbig W. Virus inhibition by Echinacea purpurea. Planta Medica 1978;33:89-102.
14. Schoneberger D. The influence of immune-stimulating effects of pressed juice from Echinacea purpurea on the course and severity of colds. Results of a double-blinded study. Forum Immunologie 1992;8:2-12.
15. Coeugniet EG, Kuhnast R. Recurrent candidiasis. Adjuvant immunotherapy with different formulations of Echinacin. Therapiewoche 1986;36:3352-3358.
16. Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing and treating the common cold (Cochrane Review). IN: The Cochrane Library, Issue 3, 1999. Oxford, UK.
17. Muldner VH, Soller M. Antidepresinve wirkung eines auf den wirkstoffkomplex hypericin standardisierten hypericum-extrakes. Arzneim Forsch 1984;34:918.
18. Lavie D. Antiviral pharmaceutical compositions containing hypericin or pseudohypericin. European Patent Application 87111467.4, filed 8/8/87, European Patent Office. Publ No. 0 256 A2. 175-177, 1987.
19. Barbagallo C, Chisari G. Antimicrobial activity of three Hypericum species. Filoterapia 1987;58:175-77.
20. Cooper WC, James J. An observational study of the safety and efficacy of hypericin in HIV+ subjects. Int Conf AIDS 1990;6: 369 (abstract no. 2063).
21. Steinbeck-Klose A, Wernet P. Successful long-term treatment over 40 months of HIV patients with intravenous hypericin. Int Conf AIDS 1993;9:470 (abstract no. PO-B26-2012).
22. Furner V, Bek M. Gold J. A Phase I/II unblinded dose ranging stury of hypericin in HIV positive subjects. Int Conf AIDS 1991;7:199 (abstract no. W.B.2071).
23. Hobbs C. St. John's Wort, Hypericum perforatum. HerbalGram 1989;18/19:24-33.
24. Hattori M, Sakamoto T, Kobashi K, Namba T. Metabolism of glycyrrhizin by human intestinal flora. Planta Med 1983;48:38-42.
25. Abe N, Ebina T, Ishida N. Interferon induction by glycyrrhizin and glycyrrhentinic acid in mice. Microbial Immunol 1982:26:535-539.
26. Pompei R, Pani A, Flore O, et al. Antiviral activity of glycyrrhizic acid. Experentia 1980;36:304-5.
27. Mitscher L, Park Y, Clark D. Antimicrobial agents from higher plants. Antimicrobial isoflavinoids from Glycyrrhiza glabra. J Nat Products 1980;43:259-269.
28. Suzuki H, Ohta Y, Takino T, et al. Effects on glycyrrhizin on biochemical tests of patients with chronic hepatitis - double blind trial. Asian Med J 1984;26:423-438.
29. Eisenburg J. Treatment of chronic Hepatitis B. Part 2. Effect of glycyrrhizic acid on the course of illness. Fortschr Med 1992;110:395-8.
30. Partiridge M, Poswillo D. Topical carbonoxolone sodium in the management of herpes simplex infection. Br J Oral Maxillofac Surg 1984;22:138-145.
31. Csonka G, Tyrrell D. Treatment of herpes genitalis with carbonoxolone and cicloxolone creams. A double blind placebo controlled trial. Br J Ven Dis 1984:60:178-181.
32. Larsson B, Jonasson A, Fianu S.Prophylactic effect of UVA-E in women with recurrent cystitis: A preliminary report. Curr Ther Res 1993;53:441-3.

Jacksonville Medicine / February, 2001

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